Dammarane-Type Triterpenoids from the Stembark of Aglaia Argentea (Meliaceae)

Jurnal Kimia VALENSI: Jurnal Penelitian dan Pengembangan Ilmu Kimia, 4(1), Mei 2018, 7-13

Available online at Website: http://journal.uinjkt.ac.id/index.php/valensi Dammarane-Type Triterpenoids from The Stembark of Aglaia argentea (Meliaceae)

Ace Tatang Hidayat1,2, Kindi Farabi1, Ida Nur Farida2, Kansy Haikal2, Nurlelasari1, Desi Harneti1, Rani Maharani1,2, Unang Supratman1,2, Yoshihito Shiono3

1Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor 45363, Indonesia 2Central Laboratory of Universitas Padjadjaran, Jatinangor 45363, Indonesia 3Department of Food, Life, and Environmental Science, Faculty of Agriculture, Yamagata University, Tsuruoka, Yamagata 997-8555, Japan

E-mail: [email protected]

Received: January 2018; Revised: February 2018; Accepted: February 2018; Available Online: May 2018

Abstract

Two dammarane-type triterpenoids, 20S,24S-epoxy-3α,25-dihydroxydammarane (1) and 3α-acetyl-20S,24S- epoxy-3α,25-dihydroxydammarane (2), have been isolated from the stembark of Aglaia argentea. The chemical structure of compounds (1 and 2) were identified by spectroscopic evidences including UV, IR, 1D-NMR, 2D- NMR and MS as well as by comparing with previously reported spectral data. Those compounds were isolated from this plant for first time. Compounds (1 and 2) showed cytotoxic activity against P-388 murine leukemia cells with IC50 values of 23.96 and 8.14 M, respectively.

Keywords: Aglaia argentea, Aglaia, dammarane-type triterpenoids, Meliaceae, P-388 Murine leukemia cells.

DOI: http://dx.doi.org/10.15408/jkv.v4i1.7065

1. INTRODUCTION and C-24, a five-membered lactone ring usually appears between C-21 and C-23, and a Dammarane-type triterpenoids widely six-membered ring with epoxy bond displays distributed in various medicinal plants and between C-20 and C-25 for dammarane-type have a great amount of interest in the field of triterpenoids (Phan et al., 2011). They are new drug research and development (Zhao et usually classified into protopanaxdiol and al., 2007). Dammarane-type triterpenoids protopanaxtriol (with 6-OH) groups based on belong to tetracyclic ring triterpenoids and their aglycone moieties. Furthermore, in their structural characteristic is with H-5α, pharmacological research, dammarane-type triterpenoids, as well as their derivatives, CH3-8, H-9α, CH3-10β, H-13β, CH3-14α, C-17β side chain, and 20R or S configuration showed various bioactivities such as antitumor, and usually, C-3, C-6, C-7, C-12, C-20, C-23, antiinflammatory, immunostimulatory, C-24, or C-25 are replaced by hydroxyl group; neuronal cell proliferatory, antiaging, C-3, C-6, or C-20 are substituted by saccharide antibacterial, antidiabetes, and antiosteoporosis groups and olefinic bond are formatted abilities (Jin et al., 2011). between C-5 and C-6, C-20 and C-21, C-20 The genus Aglaia is the largest genus and C-22, C-22 and CC-23, C-24 and C-25 or of the family of Meliaceae comprises more C-25 and C-26 (Liu et al., 2011). Moreover, than 100 species distributed mainly in India, cyclization generally displays at C17-side Indonesia, Malaysia, and parts of the Western chain. Specifically, a five-membered ring with Pacific region (Leong et al., 2016). Some epoxy bond is usually formed between C-20 species of Aglaia have been phytochemically investigated previously with major constituents

Copyright©2018, Published by Jurnal KimiaVALENSI: Jurnal Penelitian dan Pengembangan Ilmu Kimia, P-ISSN: 2460-6065, E-ISSN: 2548-3013 Jurnal Kimia VALENSI, Vol. 4, No. 1, Mei 2018 [7-13] P-ISSN : 2460-6065, E-ISSN : 2548-3013

of dammarane-type triterpenoids (Zhang et al., suspended to water (500 mL) and successively 2010; Harneti et al., 2012) and cycloartane- extracted with n-hexane (2×1 L), ethyl acetate type triterpenoids (Awang et al., 2012; Leong (2×1 L) and n-butanol (2×1 L) to afford n- et al., 2016) and glabretal-type triterpenoids hexane (27 g), ethyl acetate (16 g) and n- (Su et al., 2006). In our continous search for BuOH (36 g) extracts, respectively. The n- novel secondary metabolites from Indonesian hexane soluble fraction (26.3 g) was separated Aglaia plants, we isolated and described by vacum liquid chromatography on silica gel triterpenoids, aglinone and aglinin E, from the 60 using a gradient n-hexane and EtOAc to bark of A. smithii (Harneti et al., 2012), and give nine fractions (A–I). Fraction B (2.50 g) protolimonoid from the stembark of was chromatographed on a column of silica A. argentea (Farabi et al., 2017). In the further gel, eluted with a gradient of n-hexane–EtOAc screening for novel triterpenoid compounds (10:0–1:1), to give six subfractions (C01– from Indonesia Aglaia plants, we found that C06). Subfraction C03 (250 mg) was the n-hexane of A. argentea exhibited the chromatographed on a column of silica gel, presence of triterpenoids. We report herein the eluted with CH2Cl2:CHCl3 (9.5:0.50), to give isolation, structural elucidation of dammarane- five subfractions (C03A-C03D). Subfraction type triterpenoid compounds (1-2). C03C was separated on preparative TLC on silica gel GF254, eluted with n-hexane:EtOAc 2. MATERIAL AND METHODS (8.5:1.5), to give 1 (15.2 mg). Fraction C and D were combined (1.80 g) and was General Experimental Prosedure chromatographed on a column of silica gel, Melting points were measured on an eluted with a gradient of n-hexane–EtOAc electrothermal melting point apparatus and are (10:1–1:10), to give seven subfractions (D01– uncorrected. The IR spectra were recorded on D07). Subfraction D05 (340 mg) was a Perkin-Elmer spectrum-100 FT-IR in KBr. chromatographed on a column of silica gel, Mass spectra were obtained with a Synapt G2 eluted with a gradient of n-hexane–EtOAc mass spectrometer instrument. NMR data (10:1–1:10) to afford four subfractions (D05A- were recorded on a JEOL ECZ-600 D05D). Subfraction D05C was spectrometer at 600 MHz for 1H and 150 MHz chromatographed on a column of silica gel, 13 for C and JEOL JNM A-500 spectrometer at eluted with a gradient of CHCl3–EtOAc (10:1– 500 MHz for 1H and 150 MHz for 13C, 1:10) to give 2 (10.5 mg). chemical shifts are given on a  (ppm) scale and tetramethylsilane (TMS) as an internal 3. RESULTS AND DISCUSSION standard. Column chromatography was conducted on silica gel 60 (Kanto Chemical The methanolic extract from the dried Co., Inc., Japan). TLC plates were precoated stembark of A. argentea was concentrated and with silica gel GF254 (Merck, 0.25 mm) and extracted successively with n-hexane, ethyl detection was achieved by spraying with 80% acetate, and n-butanol. The n-hexane exhibited H2SO4 in water, followed by heating. the presence of triterpenoid compounds. By using triterpenoid test to guide separations, the Plant Material n-hexane fraction was separated by The stembark of A. argentea were combination of column chromatography on collected in Bogor Botanical Garden, Bogor, silica gel and preparative TLC on silica gel West Java Province, Indonesia in June 2015. GF254 to afford two dammarane-type The plant was identified by the staff of the triterpenoids (1-2). Bogoriense Herbarium, Bogor, Indonesia and a voucher specimen (No. Bo-1288718) was 20S,24S-epoxy-3α,25-dihydroxydammarane deposited at the Herbarium. (1) White crystal, melting points 166-167 Extraction and Isolation °C; IR (KBr) vmax 2866, 3457, 1457, 1380, -1 1 13 The dried and powdered of A. 1055 cm ; H-NMR (CDCl3, 600 MHz), C- argentea (2.5 kg) was extracted with methanol NMR (CDCl3, 150 MHz), See Table 1; ESI- + (14 L) at room temperature for 5 days. After MS m/z 461.36 [M+H] , (calcd. for C30H52O3 removing the solvent, the methanol extract m/z 460.39). (133.5 g) was recovered. The extract was then

Dammarane-Type Triterpenoids from the Stembark of Aglaia argentea (Meliaceae) Hidayat, et. al.

3 3α-acetyl-20S,24S- epoxy-3α,25- oxygenated sp methine at H 3.38 (1H, t, dihydroxydammarane (2) J=3.0 Hz) and an oxygenated sp3 methine in

Solid amorphous powder; IR (KBr) part of tetrahydrofuran ring at H 3.62 (1H, dd, -1 1 vmax 3200, 2949, 1705, 1457, 1380, 1080 cm ; J=4.8, 10.2 Hz) were also obsereved in the H- 1 13 H-NMR (CDCl3, 500 MHz); C-NMR NMR spectra, supporting the presence of (CDCl3, 125 MHz), see Table 1; HR-TOFMS dammarane-type triterpenoid structure in - m/z 501.3770 [M-H] , (calcd. for C32H54O4 m/z compound (1) (Roux et al., 1998). 502,4022). 13C-NMR spectrum of (1) showed thirty carbon resonances which were classified by their chemical shifts and the DEPT spectrum as eight methyls, ten methylenes, six methines and six quarternary carbons, indicating the presence of dammarane-type triterpenoid (Harneti et al., 2014). The

presence of eight methyl resonances at C15.6 (CH3-30), 16.2 (CH3-18), 16.6 (CH3-19), 22.2 (CH3-28), 24.1 (CH3-26), 27.3 (CH3-21), 27.9 (CH3-27), and 28.4 (CH3-29), as well as two oxygenated quartenary carbon at C 86.7 and 70.3, supporting the presence of dammarane- type triterpenoid with addition of tetrahydrofuran ring (Roux et al., 1998). In order to clarify the position of functional groups in compound (1), 1H-1H COSY and HMBC experiments were carried out and the results was shown in Figure 1. The 1H-1H COSY spectrum of 1 displayed the correlations in C1-C2-C3, C5-C6-C7, C9-C11-C12- C13, C14-C15-C16-C17, and C22-C23-C24, supporting the presence of dammaran-type triterpenoid structure in (1). In the HMBC spectrum, the correlations arising from the tertiary methyl protons to their neighboring carbons enabled the assignment of the eight Compound (1) was isolated as a white o singlet methyls at C-4 (2), C-8, C-10, C-14, needle crystal, melting points, 166-167 C. The C-20, C-26, and C-27, respectively. A molecular formula of (1) was established to be methylene protons at  1.55 and methyl C H O based on of ESI-MS spectra (m/z H 30 52 3 protons at  0.82 (CH -29) were correlated to 461.36 [M+H]+, calcd. for C H O m/z H 3 30 52 3 oxygenated carbon at  76.4 (C-3), indicated 460.39) along with NMR data (Tabel 1), thus C that a secondary hydroxyl group was attached requiring five degrees of unsaturation. The UV spectrum showed no conjugated double based at C-3. Methyl protons at H 1.17 and 1.09, as on the absorption maximum above 200 nm. IR well as an oxygenated methine at H 3.62 were spectrum of (1) showed the presence of a correlated to oxygenated carbon at C 70.3 hydroxyl group (3457 cm-1), an aliphatic bands (C-25), indicated that a tertiary alcohol and an (2866 cm-1), a gem-dimethyl (1457 and 1380 isopropyl group were attached at C-25 and -1 -1 cm ) and an ether group (1055 cm ). C-24, respectively. A methine proton at H 1 H-NMR spectrum showed the 1.44 was correlated to C-20 (C 86.7), whereas presence of eight tertiary methyl signals at H the methyl proton at H 1.13 was correlated to 0.82 (3H, s, CH3-28), 0.84 (3H, s, CH3-18), C-20 (C 86.7), C-17 (C 49.8), and C-22 (C 0.87 (3H, s, CH3-19), 0.92 (3H, s, CH3-29), 35.3), indicated that a tetrahydrofuran ring was 0.95 (3H, s, CH3-30), 1.09 (3H, s, CH3-26), attached at C-17. The presence of a 1.13 (3H, s, CH3-21) and 1.17 (3H, s, CH3-27), tetrahydrofuran ring at C-17 was supported which characteristic for dammarane-type also by correlation between a methylene proton triterpenoid (Harneti et al., 2014). An at H 1.85 and C-24 (C 86.3).

Jurnal Kimia VALENSI, Vol. 4, No. 1, Mei 2018 [7-13] P-ISSN : 2460-6065, E-ISSN : 2548-3013

(1) (2)

Figure 1. Selected 1H-1H COSY and HMBC correlations for Compounds (1) and (2)

Relative stereochemistry of compound ESI-HRTOFMS spectra (m/z 502.4022 + (1) was determined on the basis of coupling [M+H] , calcd. for C30H52O3 m/z 502.4022) constant (3J) and chemical shift in the 1H and together with NMR data (Tabel 1), thus 13C-NMR spectra. A methine proton at C-3 has requiring six degrees of unsaturation. The UV a 3J 3.0 Hz, indicating that H-2 and H-3 has spectrum showed no conjugated double based axial-equatorial orientation, consequently on the absorption maximum above 200 nm. IR 3-OH has -orientation (Zhang et al., 2010; spectrum of (2) showed the presence of a Farabi et al., 2017). A detail analysis of NMR hydroxyl group (3200 cm-1), an aliphatic bands spectra with side chain of 20,34-epoxy-25- (2949 cm-1), a gem-dimethyl (1457 and 1380 -1 -1 hydroxy, indicated that C values can be used cm ) and an ether group (1080 cm ). for determining of 24R and 24S isomer, where A NMR spectra of (2) was very similar

C 83.2 for R isomer and 86.5 for S isomer. In to those of (1), the main differences are the addition, the chemical shift and coupling absence one of the hydroxyl group and the constant of H-2 can be used also for presence of an acetyl group at [C 171.1 (s), determining 24R and 24S isomer with chemical 21.5 (q) and H 2.08 (3H, s)]. In order to shift H 3.7 (1H, t, J=7.0 Hz) and H 3.6 (1H, determine the position of newly acetyl group, dd, J=5.5, 10.0 Hz), respectively (Roux et al., HMBC experiment was carried, as the results 1998; Harneti et al., 2012; Harneti et al., was shown in Figure 1. In the HMBC 2014). Compound (1) showed the chemical spectrum, a methyl proton at H 2.08 was shift for C-23 and H-24 [C 86.3 and H 3.62 correlated to carbonyl ester at C 171.1, (1H, dd, J=4.8, 10.2 Hz), as well as C 86.7 for whereas the oxygenated methine at H 4.61 C-20, consequently configuration for C-20 and was correlated also to carbonyl ester at C C-24 are S orientation. 171.1, indicating that an acetyl group was A comparison of the NMR data of (1) attached at C-3. with those of 20S,24R-epoxy-25- A detailed comparison of the NMR hydroxydammarane isolated from A. foveolata spectra of (2) to those of 3α-acetil-20S,24S- (Roux et al., 1998) revealed that the structures epoxy-25-hydroxydammarane isolated from of the two compounds are closely related, the A. foveolata (Roux et al., 1998) revealed that main differences is the chemical shift of C-24 the structures of the two compounds are very

(C 83.3), whereas compound (1) was C 86.3, similar, consequently compound (2) was consequently compound (1) was identified as identified as 3α-asetil-20S,24S-epoxy-25- 20S,24S-epoxy-25-hydroxydammarane, which hydroxydammarane, which showed from this showed from this plant for the first time. plant for the first time. Compound (2) was isolated as a solid The cytotoxicity effects of the two amorphous powder. The molecular formula of isolated compounds (1 and 2) against the (2) was established to be C32H54O4 based on of P-388 murine leukemia cells were conducted

Dammarane-Type Triterpenoids from the Stembark of Aglaia argentea (Meliaceae) Hidayat, et. al.

according to the method described in previous 25-hydroxydammarane (2) showed stronger paper (Harneti et al., 2012; Harneti et al., activity than 20S,24S-epoxy-25- 2014; Farabi et al., 2017) and were used an hydroxydammarane (1), indicated that the Artonin E (IC50 0.75 µg/mL) as a positive presence of an acetyl group increase the control (Farabi et al., 2018; Hidayat et al., cytotoxic activity in dammarane-type 2017). Cytotoxic activity of two dammarane- triterpenoid sctructure. type triterpenoids, 3α-asetil-20S,24S-epoxy-

Table 1. NMR data for Compounds (1 and 2)

Position of (1)* (1)** Carbon 13C NMR 1H NMR 13C NMR 1H NMR

C (mult.) H (Integ. Mult., J=Hz) C (mult.) H (Integ. Mult., J=Hz) 1 33.7 (t) 1.42 (1H, m) 34.3 (t) 1.40 (1H, m) 1.54 (1H, m) 1.56 (1H, m) 2 25.4 (t) 1.55 (1H, m) 24.8 (t) 1.56 (1H, m) 1.62 (1H, m) 1.61 (1H, m) 3 76.4 (d) 3.38 (1H, t, 3.0) 78.5 (d) 4.61 (1H, t, 3.0) 4 37.3 (s) - 36.8 (s) - 5 49.6 (d) 1.24 (1H, m) 50.6 (d) 1.42 (1H, dd, 3.0, 12.0) 6 18.3 (t) 1.39 (1H, m) 18.2 (t) 1.38 (1H, m) 1.54 (1H, m) 1.53 (1H, m) 7 34.8 (t) 1.63 (1H, m) 35.3 (t) 1.65 (1H, m) 1.74 (1H, m) 1.76 (1H, m) 8 40.7 (s) - 40.6 (s) - 9 50.7 (d) 1.44 (1H, dd, 2.4, 5.2) 50.8 (d) 1.20 (1H, dd, 2.6, 5.8) 10 37.7 (s) - 37.2 (s) 11 21.7 (t) 1.53 (1H, m) 21.7 (t) 1.52 (1H, m) 1.24 (1H, dd, 5.2, 7.0) 1.27 (1H, dd, 4.6, 6.5) 12 27.1 (t) 1.75 (1H, m) 27.1 (t) 1.78 (1H, m) 1.82 (1H, dd, 4.4, 7.0) 1.84 (1H, dd, 6.5, 7.2) 13 42.8 (d) 1.62 (1H, dd, 4.4, 6.2) 42.8 (d) 1.65 (1H, dd, 7.2, 10.8) 14 50.2 (s) - 50.2 (s) - 15 31.5 (t) 1.04 (1H, m) 31.6 (t) 1.05 (1H, dd, 6.2, 9.8) 1.24 (1H, m) 1.48 (1H, m) 16 25.9 (t) 1.51 (1H, m) 25.9 (t) 1.87 (1H, m) 1.56 (1H, m) 1.92 (1H, m) 17 49.8 (d) 1.44 (1H, dd, 2.5, 6.2) 49.9 (d) 1.46 (1H, dd, 2.7, 6.8) 18 16.2 (q) 0.84 (3H, s) 15.6 (q) 0.96 (3H, s) 19 16.6 (q) 0.87 (3H, s) 16.1 (q) 0.85 (3H, s) 20 86.7 (s) - 86.7 (s) - 21 27.3 (q) 1.13 (3H, s) 27.4 (q) 1.14 (3H, s) 22 35.3 (t) 1.22 (1H, m) 35.2 (t) 1.22 (1H, m) 1.34 (1H, m) 1.35 (1H, m) 23 26.4 (t) 1.85 (1H, m) 26.4 (t) 1.87 (1H, m) 1.76 (1H, m) 1.74 (1H, m) 24 86.3 (d) 3.62 (1H, dd, 4.8, 10.2) 86.4 (d) 3.63 (1H, dd, 4.8, 10.2) 25 70.3 (s) - 70.4 (s) - 26 27.9 (q) 1.17 (3H, s) 28.0 (q) 1.18 (3H, s) 27 24.1 (q) 1.09 (3H, s) 24.1 (q) 1.10 (3H, s) 28 28.4 (q) 0.92 (3H, s) 27.9 (q) 0.82 (3H, s) 29 22.2 (q) 0.82 (3H, s) 21.8 (q) 0.86 (3H, s) 30 15.6 (q) 0.95 (3H, s) 16.7 (q) 0.90 (3H, s) 1 171.1 (s) - 21.5 (q) 2.08 (3H, s) 1 13 *(600 MHz for H and 150 MHz for C in CDCl3) 1 13 ** (500 MHz for H and 125 MHz for C in CDCl3)

Jurnal Kimia VALENSI, Vol. 4, No. 1, Mei 2018 [7-13] P-ISSN : 2460-6065, E-ISSN : 2548-3013

4. CONCLUSIONS Awang K, Hayashi H. 2012. Cytotoxic triterpenoids from the bark of Aglaia Two dammarane-type triterpenoid, smithii (Meliaceae). Phytochem. Lett. 5: 20S,24S-epoxy-25-hydroxydammarane (1) and 496–499.

3α-asetil-20S,24S-epoxy-25- Hidayat AC, Farabi K, Harneti D, Maharani R, hydroxydammarane (2) have been isolated Darwati, Nurlelasari, Mayanti T, Setiawan from the stembark of Chisocheton pentandrus. AS, Supratman U, Shiono Y. 2017. This results supported the presence of Cytotoxicity and structure activity dammarane-type triterpenoid in Aglaia genus. relationship of dammarane- Compound (2) showed stronger cytotoxic typetriterpenoids from the bark of Aglaia activity against P-388 murine leukemia cells, elliptica against P-388 murine leukemia indicated that the presence of an acetyl group cells. Natural Product Sciences. 23(4): in dammarane-type triterpenoid structure can 291-298. increase cytotoxic activity. Jin CL, Kou XG, Miao ZH. 2011. Observation of ginsenosided Rg3 combined with ACKNOWLEDGEMENTS chemotherapy as adjuvant treatment for elder nonsmall-cell lung patients. J. This investigation was supported by Xinxiang Med. Coll. 28: 229–232. Directorate General of Higher Education, Ministry of Research, Technology, and Higher Liu JP, Lu D, Li PY. 2011. Two new dammarane- Education, Indonesia (Postgraduate Grant, type triterpene saponins from red American ginseng. J. Asian Nat. Prod. 2016-2018 by Unang Supratman). We thank Res. 13: 198–204. Mrs. Suzany Dwi Elita at Department of Chemistry, Faculty of Mathemathics and Leong KH, Looi CY, Loong XM, Cheah FK, Natural Sciences, Institute Technology Supratman U, Litaudon M, Mustafa MR, Bandung, Indonesia for cytotoxicity bioassay. Awang K. 2016. Cycloart-24-ene-26-ol-3- one, a new cycloartane isolated from REFERENCES leaves of Aglaia exima triggers tumour necrosis factor- receptor 1-mediated Awang K, Loong X, Leong KH, Supratman U, caspase-dependent apoptosis in colon Litaudon M, Mukhtar MR, Mohamad K. cancer cell line. PLOS ONE. 4: 1-17. 2012. Triterpenes and steroids from the leaves of Aglaia exima (Meliaceae). Phan MG, Truong TTC, Phan TS, Matsunami K, Fitoterapia. 83: 1391–1395. Otsuka H. 2011. A new diarylheptanoid and a rare dammarane triterpenoid from Farabi K, Harneti D, Nurlelasari, Maharani R, Alnus nepalensis. Chem. Nat. Compd. 47: Hidayat AT, Awang K, Supratman U, 735–73. Shiono Y. 2017. New cytotoxic protolimonoids from the stem bark of Roux D, T MT, Adeline, T Sevenet, H Hadi, Pais Aglaia argentea (Meliaceae). M, 1998. Foveolins A dan B, dammarane Phytochemistry Letters. 21: 211-215. triterpenes from Aglaia foveolata. Phytochemistry. 49(6): 1745-1748. Farabi K, Harneti K, Nurlelasari, Maharani K, Hidayat AC, Awang K, Supratman U, Su B, Chai H, Mi Q, Riswan S, Kardono LBS, Shiono Y. 2018. New cytotoxic pregnane- Afriastini JJ, Santarsiero BD, Mesecar type steroid from the stem bark of Aglaia AD, Fransworth NR, Cordell GA, elliptica (Meliaceae). Record of Natural Swanson SM, Kinghorn D. 2006. Products. 12(2): 121-127. Activity-guided isolation of cytotoxic constituents from the bark of Aglaia Harneti D, Supriadin A, Ulfah M, Safari A, crassinervia collected in Indonesia. Supratman U, Awang K, Hayashi H. 2014. J. Bioorg. Med Chem. 14: 960-972. Cytotoxic constituents from the bark of Aglaia eximia (Meliaceae). Phytochem. Zhang F, Wang J, Gu Y, Kong Y. 2010. Lett. 8: 28–31. Triterpenoids from Aglaia abbreviata and their cytotoxic activities. J. Nat. Prod. 73: Harneti D, Tjokronegoro R, Safari A, Supratman U, 2042–2046. Loong X, Mukhtar MR, Mohamad K,

Dammarane-Type Triterpenoids from the Stembark of Aglaia argentea (Meliaceae) Hidayat, et. al.

Zhao M, Fu LW, Li N, Tang WX, Li MJ. type triterpenes isolated from Nerium Hasegawa T, Ogura H, Kataoka T, Hirose oleander and their biological activities. J. K, Ando M. 2007. The ursane-, oleanane-, Recent Progr. Med. Plants. 16: 83–107. dammarane-, lupane-, and taraxasterane-